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Intrarectal Amifostine Prevents Late Rectal Complications of Radiotherapy for Prostate Cancer

Intrarectal Amifostine Prevents Late Rectal Complications of Radiotherapy for Prostate Cancer

DETROIT—Intrarectal topical application of amifostine (Ethyol), given
as a "mini-enema," is extremely tolerable, produces no systemic
toxicity, and may be an alternative to systemic administration for
preventing rectal damage in patients undergoing radiotherapy for prostate
cancer. Results of a phase I study were reported by Edgar Ben-Josef, MD. He
is associate professor in the Department of Radiation Oncology at Wayne
State University’s Karmanos Cancer Institute in Detroit.

"With 3D conformal treatment planning, it is possible to
substantially reduce grade 3 toxicity, but at doses in the vicinity of 75
Gy, 15% to 25% of patients will still develop grade 2 or higher rectal
toxicity," Dr. Ben-Josef explained. "With conventional,
nonconformal radiotherapy, the rate of grade 3 or 4 late rectal
complications is up to 10%."

Adding shielding can keep the dose to the anterior rectal wall less than
75.6 Gy and reduce grade 2 or higher rectal toxicity to 7%, according to Dr.
Ben-Josef. The problem is that also risks shielding tumor tissue from
therapeutic dosages.

"With that problem in mind, in 1998 we started a phase I study using
a topical, intrarectal application to attempt to protect the rectum from
radiation effects. The major objective was to evaluate the feasibility of an
intrarectal application of amifostine. We were not sure if patients could
tolerate and hold the mini-enema," Dr. Ben-Josef said.

The trial was also intended to determine the maximum tolerated dose (MTD)
of intrarectal amifostine, to characterize the pharmacokinetics of
intrarectal application, and to gather some data regarding efficacy.

Study Design

Amifostine was given as an aqueous solution 30 minutes before treatment
during the first 15 days of radiotherapy. Dose escalation was from 500 mg to
2,500 mg in 500-mg cohorts. Pharmacokinetics assessments were done on days 1
and 10 of radiotherapy to see if changes in systemic absorption were induced
by changes in the rectum wall secondary to radiotherapy, such as


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